Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV), particularly the HIV-1 strain. Most currently approved therapies for HIV infection target the viral reverse transcriptase and protease enzymes. There is additionally one approved drug targeting gp41 to inhibit viral entry and one approved drug targeting the integrase enzyme. Within the reverse transcriptase inhibitor and protease inhibitor classes, resistance of HIV to existing drugs is a problem. Therefore, it is important to discover and develop new antiretroviral compounds.
The inherent genetic variation within HIV has led to the identification of many HIV mutants, commonly referred to as variants, which exhibit altered drug susceptibility. On the integrase enzyme, residues 124 and 125 are recognized as highly variable across the HIV-1 virus from infected patients found in major market and developing countries. The approximate prevalence of these integrase variants are Thr124/Thr125 (44%), Ala124/Thr125 (17%), Ala124/Ala125 (16%), Thr124/Ala125 (10%), Asn124/Thr125 (6%), and Asn124/Ala125 (1%) for viruses sequenced from major market countries reported in the Los Alamos database (http://www.hiv.lanl.gov/content/hiv-db). These integrase variants may be generated using known methods in the art and publicly available polypeptide sequences for the integrase enzyme, for example from the NL4.3 strain of HIV-1 integrase (SEQ ID NO: 1).